Stability scale and atomic solvation parameters extracted from 1023 mutation experiments.

Area of Science:

• Biophysics
• Protein Chemistry
• Computational Biology

Background:

• Protein stability is crucial for function.
• Accurate prediction of protein stability and interactions remains a challenge.
• Existing scales often struggle to capture contributions from all residue types.

Purpose of the Study:

• To develop a comprehensive amino acid stability scale.
• To correlate stability with biophysical properties like solvation and burial.
• To validate the scale's predictive power for protein-protein binding.

Main Methods:

• Derived a stability scale from 1023 mutation experiments across 35 proteins.
• Correlated residue stability with octanol-to-water transfer free energy and accessible surface area.
• Calculated atomic solvation parameters.
• Predicted protein-protein binding free energy using the new scale and parameters.

Main Results:

• Hydrophobic residue stability strongly correlates with corrected transfer free energy (r=0.95).
• Both hydrophilic and overall scales correlate well with average burial accessible surface (r=0.76 and r=0.97).
• New scale and parameters accurately predicted protein-protein binding free energy (r=0.80 and r=0.83).

Conclusions:

• The derived stability scale effectively characterizes hydrophobic contributions.
• Accessible surface area is a key factor for hydrophilic and overall stability.
• The developed scale and parameters offer accurate predictions for protein folding and binding.